Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1
<p>Abstract</p> <p>Background</p> <p>Calcium signaling plays an important role in B lymphocyte survival and activation, and is critically dependent on the inositol-1,4,5-<it>tris</it>-phosphate-induced release of calcium stored in the endoplasmic reticulum (...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-08-01
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| Series: | Molecular Cancer |
| Online Access: | http://www.molecular-cancer.com/content/8/1/59 |
| _version_ | 1818530111985549312 |
|---|---|
| author | Joab Irène Chomienne Christine Kovàcs Tünde Rowe Martin Brouland Jean-Philippe Arbabian Atousa Dellis Olivier Papp Béla |
| author_facet | Joab Irène Chomienne Christine Kovàcs Tünde Rowe Martin Brouland Jean-Philippe Arbabian Atousa Dellis Olivier Papp Béla |
| author_sort | Joab Irène |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Calcium signaling plays an important role in B lymphocyte survival and activation, and is critically dependent on the inositol-1,4,5-<it>tris</it>-phosphate-induced release of calcium stored in the endoplasmic reticulum (ER). Calcium is accumulated in the ER by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes), and therefore these enzymes play an important role in ER calcium homeostasis and in the control of B of cell activation. Because Epstein-Barr virus (EBV) can immortalize B cells and contributes to lymphomagenesis, in this work the effects of the virus on SERCA-type calcium pump expression and calcium accumulation in the endoplasmic reticulum of B cells was investigated.</p> <p>Results</p> <p>Two Sarco-Endoplasmic Reticulum Calcium transport ATPase isoforms, the low Ca<sup>2+</sup>-affinity SERCA3, and the high Ca<sup>2+</sup>-affinity SERCA2 enzymes are simultaneously expressed in B cells. Latency type III infection of Burkitt's lymphoma cell lines with immortalization-competent virus expressing the full set of latency genes selectively decreased the expression of SERCA3 protein, whereas infection with immortalization-deficient virus that does not express the EBNA2 or LMP-1 viral genes was without effect. Down-modulation of SERCA3 expression could be observed upon LMP-1, but not EBNA2 expression in cells carrying inducible transgenes, and LMP-1 expression was associated with enhanced resting cytosolic calcium levels and increased calcium storage in the endoplasmic reticulum. Similarly to virus-induced B cell immortalisation, SERCA3 expression was also decreased in normal B cells undergoing activation and blastic transformation in germinal centers of lymph node follicles.</p> <p>Conclusion</p> <p>The data presented in this work indicate that EBV-induced immortalization leads to the remodelling of ER calcium homeostasis of B cells by LMP-1 that copies a previously unknown normal phenomenon taking place during antigen driven B cell activation. The functional remodelling of ER calcium homeostasis by down-regulation of SERCA3 expression constitutes a previously unknown mechanism involved in EBV-induced B cell immortalisation.</p> |
| first_indexed | 2024-12-11T17:15:37Z |
| format | Article |
| id | doaj.art-9b4e18875b3e41e598787a2a75423f2d |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-11T17:15:37Z |
| publishDate | 2009-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-9b4e18875b3e41e598787a2a75423f2d2022-12-22T00:57:22ZengBMCMolecular Cancer1476-45982009-08-01815910.1186/1476-4598-8-59Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1Joab IrèneChomienne ChristineKovàcs TündeRowe MartinBrouland Jean-PhilippeArbabian AtousaDellis OlivierPapp Béla<p>Abstract</p> <p>Background</p> <p>Calcium signaling plays an important role in B lymphocyte survival and activation, and is critically dependent on the inositol-1,4,5-<it>tris</it>-phosphate-induced release of calcium stored in the endoplasmic reticulum (ER). Calcium is accumulated in the ER by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes), and therefore these enzymes play an important role in ER calcium homeostasis and in the control of B of cell activation. Because Epstein-Barr virus (EBV) can immortalize B cells and contributes to lymphomagenesis, in this work the effects of the virus on SERCA-type calcium pump expression and calcium accumulation in the endoplasmic reticulum of B cells was investigated.</p> <p>Results</p> <p>Two Sarco-Endoplasmic Reticulum Calcium transport ATPase isoforms, the low Ca<sup>2+</sup>-affinity SERCA3, and the high Ca<sup>2+</sup>-affinity SERCA2 enzymes are simultaneously expressed in B cells. Latency type III infection of Burkitt's lymphoma cell lines with immortalization-competent virus expressing the full set of latency genes selectively decreased the expression of SERCA3 protein, whereas infection with immortalization-deficient virus that does not express the EBNA2 or LMP-1 viral genes was without effect. Down-modulation of SERCA3 expression could be observed upon LMP-1, but not EBNA2 expression in cells carrying inducible transgenes, and LMP-1 expression was associated with enhanced resting cytosolic calcium levels and increased calcium storage in the endoplasmic reticulum. Similarly to virus-induced B cell immortalisation, SERCA3 expression was also decreased in normal B cells undergoing activation and blastic transformation in germinal centers of lymph node follicles.</p> <p>Conclusion</p> <p>The data presented in this work indicate that EBV-induced immortalization leads to the remodelling of ER calcium homeostasis of B cells by LMP-1 that copies a previously unknown normal phenomenon taking place during antigen driven B cell activation. The functional remodelling of ER calcium homeostasis by down-regulation of SERCA3 expression constitutes a previously unknown mechanism involved in EBV-induced B cell immortalisation.</p>http://www.molecular-cancer.com/content/8/1/59 |
| spellingShingle | Joab Irène Chomienne Christine Kovàcs Tünde Rowe Martin Brouland Jean-Philippe Arbabian Atousa Dellis Olivier Papp Béla Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1 Molecular Cancer |
| title | Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1 |
| title_full | Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1 |
| title_fullStr | Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1 |
| title_full_unstemmed | Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1 |
| title_short | Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1 |
| title_sort | modulation of b cell endoplasmic reticulum calcium homeostasis by epstein barr virus latent membrane protein 1 |
| url | http://www.molecular-cancer.com/content/8/1/59 |
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